The effects of various pretreatments of animals on the responsiveness of cyclic AMP-generating systems in brain will be investigated. Pretreatment will include isolation stress, cold stress, reward and punishment training, agonist or antagonist drugs, electrical stimulation or lesions in specific neuronal tracts or regions, depressant, excitatory or convulsant drugs and hormonal alterations. Attempts to correlate responsiveness of cyclic AMP-generating systems in strains of mice or rats to various centrally-mediated responses, such as sensitivity to seizures, stress and various drugs will be made. Antibodies to phosphodiesterase-catalytic and regulatory proteins will be prepared and used to investigate localization and turnover of these proteins in animals under various pretreatment regimens. Correlations between cyclic AMP and cyclic GMP levels under various conditions in brain slices will be attempted.